Ventilatory stabilization technology

ABSTRACT

A system for reducing central sleep apnea (CSA) is described in which certain methods of increasing a patient&#39;s rebreathing during periods of the sleep cycle are used. By increasing rebreathing during periods of overbreathing, the over-oxygenation which typically results from the overbreathing period can be reduced, thus reducing the compensating underbreathing period and effectively reducing the loop gain associated with the central sleep apnea. Nasal occlusion and a leak resistant oral interface provide control for gas leaks from a patent interface.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation-in-part of application Ser.No. 09/498,504 filed Feb. 3, 2000, now United States patent no.

BACKGROUND OF THE INVENTION

[0002] Central sleep apnea is a type of sleep-disordered breathing thatis characterized by a failure of the sleeping brain to generate regular,rhythmic bursts of neural activity. The resulting cessation of rhythmicbreathing, referred to as apnea, represents a disorder of therespiratory control system responsible for regulating the rate and depthof breathing, i.e. overall pulmonary ventilation. Central sleep apneashould be contrasted with obstructive sleep apnea, where the proximatecause of apnea is obstruction of the pharyngeal airway despite ongoingrhythmic neural outflow to the respiratory muscles. The differencebetween central sleep apnea and obstructive sleep apnea is clearlyestablished, and the two can co-exist. While central sleep apnea canoccur in a number of clinical settings, it is most commonly observed inassociation with heart failure or cerebral vascular insufficiency. Anexample of central sleep apnea is Cheyne-Stokes respiration.

[0003] The respiratory control system comprises a negative feedbacksystem wherein a central pattern generator creates rhythmic bursts ofactivity when respiratory chemo-receptors sensing carbon dioxide, oxygenand pH are adequately stimulated (FIG. 1). While this neural output ofthe brainstem central pattern generator to the respiratory musclesderives from a neural rhythm generated intrinsically by the centralpattern generator, the generator becomes silent if the feedback signals,related to arterial P_(CO2) and P_(O2), are not sufficiently intense. Inother words, the respiratory rhythm is generated by a conditionalcentral pattern generator which requires an adequate input stimulusderived from peripheral chemoreceptors sensing arterial P_(CO2) andP_(O2) from central chemoreceptors sensing brain P_(CO2)/pH.Furthermore, the intensity of neural activity generated by therespiratory central pattern generator depends directly upon the arterialP_(CO2) inversely on the arterial P_(O2). Thus, the central andperipheral chemoreflex loops constitute a negative feedback systemregulating the arterial P_(O2) and P_(CO2), holding them constant withinnarrow limits (FIG. 1).

[0004] This normal regulation of arterial blood gases is accomplished bya stable ventilatory output of the respiratory central patterngenerator. By contrast, central sleep apnea represents an instability ofthe respiratory control system. The instability can arise from one oftwo mechanisms, namely: (1) intrinsic failure of the respiratory centralpattern generator in the face of adequate stimulation by respiratorychemoreceptors; or (2) lack of adequate stimulation of the centralpattern generator by respiratory chemoreceptors. The former is referredto as the “intrinsic instability” and the latter is referred to as the“chemoreflex instability.” Theoretically, both mechanisms can co-exist.The common form of central sleep apnea is thought to be caused by thechemoreflex instability mechanism.

[0005] The chemoreflex control of breathing might exhibit instabilityeither because the delay of the negative feedback signal is excessivelylong or because the gain of the system is excessively high. Currentevidence indicates that the latter constitutes the principal derangementin central sleep apnea caused by heart failure. Specifically, theoverall response of the control system to a change in arterial P_(CO2)is three-fold higher in heart-failure patients with central sleep apneathan in those having no sleep-disordered breathing. This increased gainprobably resides within the central chemoreflex loop; however, high gainof the peripheral chemoreflex loop cannot be excluded. Accordingly, thefundamental mechanism of central sleep apnea is taken to be high loopgain of the control system, which results in feedback instability duringsleep.

[0006] Central sleep apnea causes repeated arousals and oxyhemoglobindesaturations. Although firm evidence linking central sleep apnea tomorbidity and mortality is lacking, a variety of evidence leads to theinference that central sleep apnea may promote cardiac arhythmias,strokes, or myocardial infarctions. The repeated nocturnal arousals arelikely to impair daytime cognitive function and quality of life. Notreatment has become established as being effective for central sleepapnea. Stimulating drugs such as theophyline may be helpful, andcarbonic anhydrase inhibitors may relieve central sleep apnea in normalssleeping at high altitude. Nasal continuous positive airway pressure maydirectly or indirectly improve ventilatory stability. Increasinginspired fractional concentration (F) of oxygen in the inspired gasgenerally does not eliminate central sleep apnea, whereas increasinginspired F_(CO2) (F_(|CO2)=0.01-0.03) promptly eliminates central sleepapnea. However, long-term exposure to high F_(|CO2) would appear to bean undesirable long-term therapy.

SUMMARY OF THE PRESENT INVENTION

[0007] The present invention is a method for varying the efficiency ofpulmonary gas exchange by using a controlled amount of rebreathingduring certain periods of the central sleep apnea respiration cycle soas to counteract the effects of the transient excessive ventilation onthe level of carbon dioxide and oxygen in the lungs and in the arterialblood. In effect, this strategy is an attempt to stabilize breathing byminimizing oscillations in the feedback variables.

[0008] The invention counteracts periodic breathing due to central sleepapnea by decreasing loop gain of the respiratory control system. In oneembodiment, the invention dynamically modulates efficiency of pulmonarygas exchange in relation to pulmonary ventilation. When pulmonaryventilation is stable at resting values, the performance of the systemis unchanged. However, during a period of hyperpnea, i.e. whenventilation increases transiently to supra-normal levels, the system ismade more inefficient, thus decreasing loop gain and stabilizing thesystem.

[0009] Rebreathing can be used to increase the inspired percentagecarbon dioxide and reduce the inspired percentage oxygen just before orduring the period of overbreathing. In one embodiment, the patient'sventilation is continuously monitored and analyzed in real time so thatthe ventilation periodicities of the central sleep apnea breathing canbe detected and the inspired carbon dioxide and oxygen concentrationsadjusted appropriately by varying the amount of exhaled gas that isreinspired.

[0010] In another embodiment of the present invention, a rebreathingapparatus is a part of a nasal continuous positive airway pressure(CPAP) system. The use of continuous positive airway pressure may have abeneficial effect on cardiac function in patients with congestive heartfailure. In the future it is likely that patients with congestive heartfailure will receive nasal CPAP for treatment of the heart failure.Central sleep apnea may not immediately disappear upon administration ofconventional nasal CPAP therapy as central sleep apnea respiration isbasically of a non-obstructive origin. However, over a period of aboutfour weeks the degree of heart failure improves; thus, the resultingcentral sleep apnea respiration may be relieved by the continuouspositive airway pressure. This is described in the papers, Naughton, etal., “Effective Continuous Positive Airway Pressure on Central SleepApnea and Nocturnal Percentage Carbon Dioxide in Heart Failure,”American Journal Respiratory Critical Care Medicine, Vol. 1509, pp1598-1604, 1994; Naughton, et al., “Treatment of Congestive HeartFailure and Central Sleep Apnea Respiration during Sleep by ContinuousPositive Airway Pressure,” American Journal of Critical Care Medicine,Vol. 151, pp 92-97, 1995; and, Naughton, et al., “The Role ofHyperventilation in the Pathogenesis of Central Sleep Apneas in Patientswith Congestive Heart Failure,” American Review of Respiratory Diseases,Vol. 148, pp 330-338, 1993.

[0011] It is desirable to have a prompt elimination of the central sleepapnea respiration because the resulting daytime sleepiness and impairedcognition resulting from repeated arousals impair the patient's qualityof life. Immediately relieving central sleep apnea breathing during theCPAP treatment would have the advantage that the patient wouldexperience a better sleep and would be more rested. This in turn wouldenhance compliance with the CPAP treatment program. Conventional nasalCPAP provides no immediate relief of central sleep apnea respiration andresulting arousals.

[0012] A conventional CPAP system is modified in one embodiment of thepresent invention to allow a controlled amount of rebreathing during aportion of the central sleep apnea respiration cycle. In thisembodiment, a valve is used to control the amount of rebreathing. Whenthe valve is closed, rebreathing occurs and when the valve is open norebreathing occurs. A computer connected to a flow meter can be used todetect periodicities in the central sleep apnea respiration cycle. Thecomputer can then control the valve to open and close. Nasal occlusionin combination with an oral appliance may be used to guaranteecontrolled re-breathing.

[0013] Another embodiment of the present invention concerns a passivelow-bias-flow device for treating central sleep apnea. This apparatusincludes a gas-supply means, such as a blower, and a patient interfacethat is fitted to a patient's airway. The gas-supply means is adjustedso that air flow from the gas-supply means is such that for thepatient's normal breathing, the gas flow supplied by the gas-supplymeans is sufficient to prevent a significant amount of the patient'sexhaled gases from flowing retrograde into a tube between the gas-supplymeans and the patient interface. During periods of increased breathingpreceding or following central sleep apnea, the preset air flow is suchthat some of the patient's exhaled gases flow retrograde into the tube.Some of the exhaled gases flowing retrograde into the tube will berebreathed by the patient. Thus, during periods of overbreathingassociated with central sleep apnea, there will be some rebreathing ofgases containing a higher F_(CO2) and a lower F_(O2) than room air. Notethat conventional CPAP systems are set such that there is no retrogradeair flow any time in the sleep cycle.

[0014] Yet another embodiment of the present invention is a method foradjusting an apparatus comprising a gas-supply means, a patientinterface and a tube between the patient interface and the gas-supplymeans. In this method, the patient interface is fitted to the patient'sairway. The supply of gas from the gas-supply means is set high enoughthat during the patient's normal breathing, the gas flow supplied by thegas-supply means is sufficient to prevent a significant amount of thepatient's exhaled gases from flowing retrograde into the tube, but setlow enough that during periods of increased breathing increased withcentral sleep apnea, some of the patient's exhaled gases flow retrogradeinto the tube.

[0015] Still another embodiment of the present invention concerns anapparatus for treating central sleep apnea wherein the supply of gasfrom a gas-supply means has a varying gas pressure that changes atdifferent times during the patient's sleep cycle. In this way,rebreathing can be increased. For example, in one embodiment, the gaspressure from the blower is decreased during periods of increasedbreathing associated with central sleep apnea so that some of thepatient's exhaled gases flow retrograde between the patient interfaceand the blower. This approach is less advantageous because users oftenfind the varying patient interface pressure to be annoying. Also,varying of the patient interface pressure can affect the internal deadspace in a manner counter to the rebreathing effect.

[0016] The general approach is that the blower pressure is set at aminimum level that eliminates all evidence of upper airway obstruction,or at a level deemed appropriate for treating heart failure. The biasflow is then reduced to a level that eliminates central sleep apneawithout increasing the external dead space during unstimulatedbreathing. The bias flow can then be fixed at this level or variedsystematically within or between cycles of periodic breathing.

BRIEF DESCRIPTION OF THE DRAWINGS

[0017] There will now be described preferred embodiments of theinvention, with reference to the drawings, in which:

[0018]FIG. 1 is a diagram illustrating central sleep apnea;

[0019]FIG. 2 is a diagram illustrating one embodiment of the rebreathingapparatus of the present invention;

[0020]FIG. 2A is a diagram illustrating use of the embodiment of FIG. 2with a dental appliance;

[0021]FIGS. 2B and 2C illustrate two embodiments of an oral appliance ofFIG. 2A;

[0022]FIG. 3 is a diagram illustrating central sleep apnea respiration;

[0023]FIG. 4A is a diagram of one embodiment of the present inventionusing a passive loop gain modulation for ventilization stabilizationusing a single pre-set gas flow pressure from a blower;

[0024]FIG. 4B is a diagram of an alternate embodiment of the system ofFIG. 4A using a flow meter and a computer;

[0025]FIG. 5 is a diagram of one embodiment of the present inventionwhich uses computer control of the blower pressure to modify the ventpressure from the blower during certain periods of a sleep cycle;

[0026]FIG. 6 is a diagram of an embodiment of the present inventionwhich uses computer control of a dead space attached to valves so as tocause rebreathing during certain periods of a sleep cycle;

[0027]FIG. 7 is a diagram of one embodiment of the present inventionusing a recirculator to increase rebreathing during certain periods of asleep cycle;

[0028]FIGS. 8A-8F are diagrams depicting air flow accorded in tubingconnecting between the blower and the mask;

[0029]FIG. 9 depicts the changes in V_(ret) and V_(wash) that occur whenpulmonary ventilation is stimulated by increasing arterial P_(CO2);

[0030]FIGS. 10, 11 and 12 are diagrams that illustrate the dependence ofV_(ret), V_(ED) and T_(FRAC) on V _(E);

[0031]FIG. 13 is a diagram that illustrates the relationship of V _(A)and V _(E) at the four levels of V _(B);

[0032]FIG. 14 is a diagram illustrating the general dependence of theloop gain on the ratio log V _(E)/V _(A);

[0033]FIG. 15 is a diagram that illustrates the breathing air flow inthe tube of a conventional CPAP system;

[0034]FIG. 16 is a diagram that illustrates the normal breathing flow inthe tube of the embodiment of FIG. 4A;

[0035]FIG. 17 is a diagram that illustrates overbreathing flow in thetube in the embodiment of FIG. 4A;

[0036]FIG. 18A is a diagram of an embodiment of the present invention inwhich the size of the exit tube of the mask is varied slowly over thepatient's sleep cycle;

[0037]FIG. 18B is a graph illustrating one example of changing of theexit hole size during the night, for the apparatus of FIG. 18A; and

[0038]FIG. 19 is a diagram of an alternate embodiment using the bloweroutput as an active control device to adjust the level of rebreathing bya patient.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0039]FIG. 2 is a diagram illustrating the rebreathing apparatus of oneactive control embodiment of the present invention. In this embodiment,a continuous positive airway pressure apparatus including blower 20,tube 22 and patient interface 24 is used. Patient interface 24, forexample a mask or oral interface, preferably produces an airtight tightseal to the face for use in the continuous positive airway pressuretreatment. A discussion of continuous positive airway pressure and apreferred continuous positive airway pressure apparatus is described inRemmers, et al. U.S. Pat. No. 5,645,053, “Auto-CPAP Systems and Methodfor Preventing Patient Disturbance Using Airflow Profile Information.”In conventional CPAP, a blower is used to maintain a relatively highconstant pressure in a mask and to provide a bias flow of fresh air fromthe blower out the mask.

[0040] In one embodiment of the present invention, tube 26 is connectedto the exhaust port 31 of the patient interface and conducts gas to thevariable resistor 28. Alternatively, the valve can be located on theexhaust port of the patient interface. Tube 22 is used as a dead spacefor rebreathing during some periods of the central sleep apnearespiration. When the valve 28 is open, no rebreathing occurs becauseall the exhaled gas is carried out tube 26 through valve 28 by the biasflow before inspiration occurs. When valve 28 is closed, the bias flowceases and no expired air is conducted through tube 26. In this case,some partial rebreathing occurs because the expired air is conductedretrograde up tube 22 to the blower. The gases in the tube 26 have ahigher concentration of carbon dioxide and a lower concentration ofoxygen than room air. When the patient inspires, gas is conducted fromthe blower to the patient and the previously expired gases are inhaledby the patient.

[0041] Normally, the bias flow of gas from the blower through thepatient interface and out port 30 would be adequate to completely purgethe system during the expiratory phase of the respiratory cycle so thatno gas expired by the patient remains in the system. Thus, the gasinspired by the patient had a composition of room air (O₂ concentration21%; CO₂ concentration about 0%). Conversely, if the bias flow isreduced to zero by completely occluding port 30 with valve 28, the gasexhaled by the patient would fill the tube 22 connecting the patientinterface to the blower. Such expired gas would typically have a carbondioxide concentration of 5% and an oxygen concentration of 16%. Uponinhalation, the patient would first inspire the high carbon dioxide, lowoxygen mixture filling the tube, followed by inhalation of room air fromthe blower. Depending upon the length of the tubing this mixture couldamount to rebreathing of 20 to 60 percent of the tidal volume. Byvarying the exhaust port outflow resistance, the degree of rebreathingbetween these limits can be varied and the inspired concentration ofcarbon dioxide and oxygen can be manipulated. In one embodiment, flowmeter 32 connected to computer 34 is used to detect the flow of gases toand from the blower 20. The computer 34 is used to identify theperiodicities in pulmonary ventilation caused by the central sleep apnearespiration and to control the valve 28 to cause rebreathing duringcertain periods of the central sleep apnea cycle.

[0042] The gas flow from the blower comprises the bias flow (patientinterface exit flow+leak flow) plus the respiratory airflow. Thecomputer monitors this flow and calculates the bias flow, leak flow,retrograde flow, retrograde expired volume and wash volume.

[0043] A computer 34 can detect the amplitude of the central sleep apneacycle and to adjust the resistance of the valve 28 according. Forexample, if there are large variations in pulmonary ventilation duringthe central sleep apnea cycle, the valve 28 can be completely closedduring the overbreathing period. If there are small variations inpulmonary ventilation during the central sleep apnea cycle, the valve 28can be partially open during the overbreathing period. Thus, a higherlevel of rebreathing will occur when the variation in pulmonaryventilation during the central sleep apnea cycle is high than will occurwhen the variation in pulmonary ventilation during the central sleepapnea cycle is low.

[0044] Because of the low impedance of the CPAP blower 20, variations ofthe resistance in the outflow line cause very little change in patientinterface pressure. Accordingly, the full range of variations in outflowresistance can be made without producing significant deviations in thedesired CPAP patient interface pressure.

[0045] The flow meter 32 and computer 34 can quantitate the level ofpulmonary ventilation. For example, the ratio of breath volume to breathperiod gives an indication of the level of the instantaneous pulmonaryventilation. Other indices such as mean or peak inspiratory flow ratecould also be used.

[0046]FIG. 3 shows an idealized diagram of the periodicities of theoverbreathing and underbreathing during central sleep apnea respiration.This diagram shows the regions of overbreathing 50 a and the regions ofunderbreathing 50 b compared to the moving time average of ventilation.The computer system will be able to determine the periodicities of thecentral sleep apnea breathing. Typically, there is about a 50-60 secondperiodicity to the overbreathing and underbreathing in the central sleepapnea breathing.

[0047] A number of techniques are used to control the degree and timingof rebreathing with the valve 28 in order to eliminate central sleepapnea. One way of controlling rebreathing so as to reduce the centralsleep apnea respiration is to anticipate the different cycles in thecentral sleep apnea respiration. For example, looking at FIG. 3, at timeA, the system will anticipate a period of overbreathing and thus beginrebreathing by closing valve 28 as shown in FIG. 2. By the timeoverbreathing portion 50 a occurs, there is some level of rebreathing.Because of this, pulmonary gas exchange becomes less efficient duringthe period of overbreathing and, thereby, the resulting rise in lungoxygen and fall in lung carbon dioxide will be less. As a result, thelevel of oxygen in the blood does not get too high and the level ofcarbon dioxide does not get too low. This stabilizes the oxygen andcarbon dioxide pressures in the arterial blood and thus will reduce theamplitude of subsequent underbreathing or the length of the apnea. Attime B, the system will anticipate an underbreathing cycle by openingthe valve 28 and rebreathing will no longer occur. The apparatus of thepresent invention can reduce central sleep apnea rebreathing (line 50)to a lower level as shown in dotted line 60 in FIG. 2. Time A and time Bfor the beginning and end of the rebreathing can be determined by thecomputer 34 shown in FIG. 2.

[0048]FIG. 4A is a diagram that illustrates a passive loop gainmodulation system for use in the present invention. FIG. 4A depicts asystem using a gas-supply means such as the air blower 60 connected to alength of input tubing 62 and then to a patient interface 64. Thissystem uses a simple fixed exit port for the patient interface. A tubingvolume greater than that normally used with obstructive sleep apnea canbe used with the present invention. For example, a ten-foot rather thansix-foot tubing can be used. The blower 60 preferably has a very lowimpedance. That is, changes in the air flow do not significantly changethe air pressure supplied by the blower. This can help maintain arelatively stable patient interface pressure even as the tube flowbecomes retrograde.

[0049] Additionally, in one embodiment, the air blower is able to supplyair pressure much lower than conventional CPAP blowers. In oneembodiment, the air blower can be adjusted to supply pressures below 4cm H₂O (preferably 2 cm H₂O or below). The ability to supply such smallpressures allows for the retrograde flow as discussed below. The patientinterface is fitted about the patient's airway. During normal breathing,the air supplied from the blower 60 and tube 62 to the patient interface64 does not cause any rebreathing because any exhaled air will beflushed before the next inhale period. During periods of heavybreathing, the preset gas flow pressure is set so that enough exhaledair flows retrograde into the tube such that during the next inhaleperiod some expired gas is rebreathed. In this embodiment, theoverbreathing occurs during certain periods of the sleep cycleassociated with central sleep apnea. Rebreathing during periods ofoverbreathing during central sleep apnea tends to reduce the resultingspike in the blood oxygen level. Thus, the period of underbreathingfollowing the overbreathing in the central sleep apnea sleep cycle willalso be reduced.

[0050] The alternating periods of under- and overbreathing are reducedby the rebreathing which takes place during the periods ofoverbreathing. The rebreathing attenuates the arterial blood oxygenspike and the reduction in arterial P_(CO2) caused by the overbreathing.Thus, there is less underventilation when the blood reaches thechemoreceptors. Thus, the amplitude of the periodic breathing isreduced.

[0051] The embodiment of FIG. 4A is different than the conventional CPAPin that the preset gas flow pressure is lower and/or the patientinterface exit hole is smaller than that used with conventional CPAPsystems. By reducing the gas flow pressure from the typical CPAP gasflow pressures, and/or reducing the patient interface exit hole size,the retrograde flow during the overbreathing periods is produced.

[0052] The system of FIG. 4A has the advantage that it does not requireactive control of the blower pressure. The patient can be checked into asleep center and the correct blower pressure and patient interface exithole size set. Thereafter, the system can be placed on the patient'sairway every night without requiring an expensive controller-basedsystem. The preset blower gas pressure depends upon the air flowresistance caused by the exit 64, the normal exhale pressure and theoverbreathing exhale pressure. If the gas-supply pressure system is anair blower 60, then by modifying the revolutions per minute of the airblower, the preset gas flow pressure can be set.

[0053] The air supply pressure for patients with central sleep apnea butwithout obstructive sleep apnea can be set at a relatively low levelsuch as below 4 cm H₂O. The normal patient interface exit holes producethe desired effect at these pressures. The end-tidal F_(CO2) andinspired F_(CO2) can be monitored by a CO₂ meter 65 with an aspirationline connected to the patient interface. Importantly, all mouth leaksshould be eliminated by using a leak resistant patient interface inorder to have expired gas move into the tubing 62. This can be achievedby applying a chin strap, or by using an oral appliance 25 (FIG. 2A)such as a full arch dental appliance applied to the upper and lowerteeth, or both. An alternative approach to difficult mouth leaks is touse a full face mask covering the mouth as well as the nose. This meansthat expired gas emanating from the nose or the mouth will travelretrogradely up the tubing 62 toward the blower. While it is importantthat leaks between the patient interface and the patient be minimized,it is also important that as much as possible of the exhaled air of thepatient be conserved and made available for re-breathing. Hence, if thepatient interface connects to the nose, then the mouth passageway shouldbe blocked, and if the patient interface connects to the mouth, then thenasal passageway should be blocked. In either case, leaks through theunused passageway should be minimized.

[0054] Examples of an oral appliance 25 are illustrated in more detailin FIG. 2B and FIG. 2C. In FIG. 2B, the oral appliance 25 is a dentalappliance. In FIG. 2B, the oral appliance 25 is designed for fittingwithin the teeth and has an upper tray 25A that fits between the lipsand teeth of a patient, and a lower tray 25B that provides a sealingsurface for the lips to rest on. An opening 25C in the center of theoral appliance 25 of FIG. 2B communicates with a CPAP hose connector 25Dto provide CPAP pressure delivery. The oral appliance 25 of FIG. 2C isfitted to a patient's mouth directly onto the lips, without using theteeth. The oral appliance 25 of FIG. 2C is held on a patient with a mask27 that fits around a patient's airway and is secured with the use ofstraps and a pad 29A at the back of the patient's head. A tube 29B withnormal bias ports 29C blocked, and low-flow bias flow port 29D, connectsto the CPAP apparatus through CPAP connection 29E. The length of thetube 29B allows for a controlled amount of rebreathing.

[0055] A feature of the mode of action of the technology described inthis patent document relates to the behaviour of the system duringhyperventilatory periods. At these times, when such a hyperventilatoryphase occurs, the patient generates a large tidal volume and shortduration of expiration. Together, these induce rebreathing of expiredgas that has flowed retrogradely into the CPAP conduit 29B connectingthe CPAP blower to the patient interface such as oral appliance 25.Patients with central sleep apnea using Low Flow CPAP nightly in thehome may find that, during periods of hyperventilation, mouth leaks mayoccur of sufficient magnitude to vitiate the rebreathing of exhaledgasses. For such patients, it is preferable to use a dental appliance 25to apply CPAP pressure to the mouth together with nasal occlusion toeliminate leaks from the nose. Data from studies on patients using adental appliance and nasal occlusion revealed that the therapy waseffective in resolving the central sleep apnea and that during hyperpnicphases no leak of exhaled gasses occurred. For effective application ofLow Flow CPAP an oral interface, such as the oral appliance 25, shouldbe used in combination with nasal occlusion. Nasal occlusion may beobtained through plugs inserted in the nostrils or an external U-shapedclamp 29F (FIG. 2C) similar to what would be used by a swimmer.

[0056] If the patient has an element of obstructive sleep apnea, thepatient interface pressure is increased progressively until all evidenceof upper airway obstruction is eliminated. If the patient is receivingnasal CPAP as treatment for heart failure, patient interface pressure isset at the desired level (typically 8-10 cm H₂O). The bias flow (patientinterface hole size) can then be reduced until central sleep apnea iseliminating without adding dead space.

[0057] For patients with heart conditions, the patient interfacepressure can be set at the valve suggested by the literature (typicallyabout 10 cm H₂O). Then the bias flow is adjusted.

[0058] The flow through tube 62 depends upon the difference in pressurebetween the blower pressure (i.e., pressure at the outlet of the blower)and patient interface pressure. Blower pressure is set by therevolutions per minute (RPM) of the blower and will be virtuallyconstant because the internal impedance of the blower is very low. Whenno respiratory airflow is occurring (i.e., at the end of expiration),patient interface pressure is less than blower pressure by an amountthat is dictated by the flow resistive properties of the connecting tubeand the rate of bias flow. This is typically 1-2 cm of water pressuredifference when bias flow is at 0.5-1.5 L/sec. When the patientinterface is applied to the patient and the patient is breathing,patient interface pressure varies during the respiratory cycle dependingupon the flow resistance properties of the connecting tube and theairflow generated by the patient. During inspiration the patientinterface pressure drops, typically 1-2 cm of water, an duringexpiration pressure may rise transiently a similar amount. During quietbreathing the peak-to-peak fluctuations in patient interface pressureare less than during heavy breathing or hyperpnea.

[0059] Thus, during quiet breathing the patient interface pressure risesduring exhalation and this reduces the driving pressure differencebetween the blower and the patient interface, thereby reducing flow inthe tube. If the expired tidal volume increases, however, peakexpiratory flow will increase and this will be associated with a furtherincrease in patient interface pressure. If patient interface pressureincreases to equal blower pressure, flow in the tube will stop. Whenpatient interface pressure exceeds blower pressure, flow in the tubewill be in a retrograde direction, i.e., from the patient interface tothe blower. Such retrograde airflow will first occur early in expirationand the volume of air which moves into the connecting tube will bewashed out later in expiration as patient interface pressure declinesand flow from the blower to the patient interface increases. However, ifbias flow is low and the tidal volume is large, a large amount ofretrograde flow will occur and a large volume of expired gas will moveinto the tube. Because the bias flow is small, the wash flow purging thetube will be small. In such a case, not all of the retrograde volumewill be washed out before the next inspiration. As a consequence, theoverall inspired gas will have a somewhat reduced oxygen concentrationand an elevated carbon dioxide concentration.

[0060]FIGS. 15-17 illustrate the flow in the tube between a blower and apatient interface. FIG. 15 is a graph that illustrates breathing airflow in the tube of a conventional CPAP system. Note that during theexhale portion, the flow from the blower to the patient interface alwaysoverpowers the exhale pressure such that there is no retrograde flowinto the tube. This is typically done by setting the air blower pressureand exhaust port resistance such that bias flow out of the patientinterface is relatively high and the possibility of retrograde flow isavoided. This normal flow occurs even for the overbreathing associatedwith central sleep apnea.

[0061]FIGS. 16 and 17 are diagrams that illustrate the effect ofbreathing in systems of the present invention in which the blowerpressure and bias flow out of the exit hole of the patient interface areset such that there is retrograde flow during portions of overbreathingassociated with central sleep apnea.

[0062]FIG. 16 illustrates the situation in which there is normalbreathing. Even with normal breathing, there is some retrograde flowduring the period 202. Later in the exhale period the retrograde volumeis washed from the tube by the normal flow that occurs during period204. Thus there is little or no rebreathing during the normal breathingperiods. The system of the present invention does not add dead spaceduring the normal breathing periods. This is important because theaddition of dead space can increase the concentration of carbon dioxidethat is supplied to the bloodstream. It is assumed that if the increasedcarbon dioxide level persists for multiple days, the body will readjustthe internal feedback system an undesirable manner.

[0063]FIG. 17 illustrates an embodiment showing overbreathing along withthe apparatus of the present invention. In the embodiment of FIG. 17,the overbreathing is such that there is some retrograde flow of exhaledgases, which remain in the tube at the time of the next inhale portion.This means that at the next inhale portion, the patient will reinspiresome exhaled gases with the resultant higher concentration of carbondioxide. Note that in FIG. 17, the initial exhale region 206 is greaterthan the exhale region 208.

[0064] In one embodiment of the present invention, the retrograde flowvolume and wash volume for the normal breathing can be used to set theoperation of the present invention. In one embodiment, the retrogradevolume region 202 should be one-half the size of the wash flow region204 for normal breathing. Other rules of thumb such as the comparisonsof the aveolar ventilation to the bias flow out of the patient interfaceand/or comparisons of the washout time to the duration of expirationcould also be used to set the operations of the system of the presentinvention.

[0065]FIG. 4B shows the device of FIG. 4A with the addition of acomputer 67 and flow meter 69. The flow meter 69 is used to detect thedesired air flow in the tube 62. The blower can then be adjusted so thatthere is retrograde flow during periods of overbreathing and noretrograde flow otherwise. The device of FIG. 4B can be used tocalibrate the device of FIG. 4A for an individual patient.

[0066]FIGS. 18A and 18B illustrate an embodiment in which the patientinterface exit size is slowly changed over the course of the night. Inthis embodiment, the blower 210 supplies airflow at a selected pressure.Flowmeter 212 is connected into the tube 214 which allows the flow inthe tube 214 to be determined along with additional parameters of thesystem including the aveolar volume, bias flow, and the like. Theprocessor 216 slowly changes the size of the exit hole using thevariable air resistance apparatus 218. Unlike the system of FIG. 2, thesize of the variable output resistance 218 is modified slowly over thenight.

[0067] Looking at FIG. 18B, if the patient has obstructive sleep apneaas well as central sleep apnea, at the beginning of the night the outputvalve can be set relatively large, increasing the bias flow out of thepatient interface and thus reducing any effect of retrograde into thetube 214. Once the obstructive sleep apnea is reduced, the valvediameter can be slowly decreased, which can cause an increase ofretrograde flow into the tube 214 during the overbreathing portion ofcentral sleep apnea and thus can cause rebreathing which can reduce thecentral sleep apnea. Additional adjustments in the patient interfacevalve opening can be made based upon calculations made by the processor216.

[0068]FIG. 5 is an embodiment of the present invention in which theblower 70 is dynamically controlled. A flow meter 72 is placed in thetube 74 between the blower 70 and patient interface 76. A flow meter canalso be placed near the patient's face. The system of FIG. 5 allowscomputer control to decrease the blower pressure during certain periodsof a sleep cycle. Thus, during periods of heavy breathing, the blowerpressure can be reduced to facilitate retrograde flow and rebreathing.This embodiment is less advantageoous because of the mixed effects ofchanges in the patient interface pressure. By modifying the gas supplypressure supplied by the blower 70, the retrograde flow into the tube 74can be increased and decreased, as desired.

[0069]FIG. 6 is an alternate embodiment of the present invention. Inthis embodiment, the patient interface 82 is connected to dead space 84by computer-controlled valves 86 and 88. The amount of rebreathingduring certain period of the sleep cycle can be modified by changingbias flow by opening and closing the valves 86 and 88, thus reducing thecentral sleep apnea.

[0070]FIG. 7 is an embodiment using a recirculator 90. During certainportions of the sleep cycle, the recirculator 90 allowing exhaled air tobe drawn in by the recirculator 90 recirculated and supplied to the userat the patient interface 92. In this manner, the central sleep apnea canbe reduced by increasing the rebreathing at selected portions of thesleep cycle.

Technical Description

[0071] One embodiment of the invention is applied in the setting ofnasal continuous positive pressure (CPAP) therapy. The loop gain of thenegative feedback respiratory control system is reduced principally byincreasing the volume of external dead space (V_(ED)), the common airwaythrough which gas is conducted during inspiration and expiration. Theexternal dead space constitutes an extension of the internal dead space(V_(ID)) comprising the airways of the lung and the upper airway. Thetotal dead space (V_(D)) equals the sum of the internal and externaldead spaces.

V _(D) =V _(ED) +V _(ID)  (Equation 1)

[0072] This volume represents an obligatory inefficiency of the controlsystem in that it reduces the portion of the tidal volume (V_(T)) thatparticipates in gas exchange within the lungs. Specifically, the tidalvolume is the sum of two components

V _(T) =V _(D) +V _(A)  (Equation 2)

[0073] where V_(A) represents the “alveolar” portion of the tidalvolume, i.e. the volume that participates in respiratory gas exchange.Also, V _(E)=V _(A)+V _(D), where the symbols V _(E), V _(A), and V _(D)signify the products f.V_(T), f.V_(A) and f.V_(D) (f representsrespiratory frequency). In the negative feedback loop of the respiratorycontrol system (FIG. 1), V _(E) represents the output of the respiratorycentral pattern generator and V _(A) is a variable which influencesarterial blood gas pressures. The link between V _(E) and V _(A) is, ofcourse, V _(D) which is the primary variable manipulated in dynamicallycontrolling loop gain.

[0074] Dynamic control of the rebreathing volume is achieved when thepatient is breathing through a nasal CPAP apparatus. When usingconventional nasal CPAP the nose is covered by a mask which is connectedto a pressure-generating source by a length of tubing. The nose mask isflushed continuously by a stream of gas flowing from the pressure sourceand exiting the exhaust port of the mask. This will be referred to asthe bias flow (V _(B)). When using nasal CPAP for its traditionalapplication, i.e., treatment of OSA, the rate of exhaust flow isrelatively high so that virtually all the expired gas which enters themask from the nose flows into the mask and out the exhaust port. Becauseof the relatively high V _(B) the mask is completely washed out beforethe next inspiration occurs. Thus, the gas inspired from the mask has acomposition equal to that flowing from the blower (typically room air:F_(|O2)=0.293; F_(|CO2)=0.0003). In this situation, typical for OSAtreatment, the nose mask adds no external dead space. The inventiondynamically increases V_(ED) by using a lower value of V _(B) and this,in turn, dynamically reduces V _(A) (Equation 2). Thus, the component ofpulmonary ventilation effective in gas exchange, alveolar ventilation (V_(A)), is altered on a moment-to-moment basis. Since V _(A) determinesthe values of the feedback variables, arterial P_(O2) and P_(CO2), V_(D) directly influences loop gain (FIG. 1). Thus, the loop gain (L.G.)of the system can be manipulated as below:

↓V _(B)→↑V_(ED)→↓V _(A)→↓L.G.  (Equation 3)

[0075] Importantly, the increase in V_(ED) occurs only during periods ofhyperpnea, as described below. Thus, during normal breathing, no deadspace is added to the system.

[0076] As secondary strategies, the invention utilizes changes in CPAPpressure to change lung volume and, thereby, influence loop gain of therespiratory control system. In particular, in increase in lung volumedecreases loop gain by decreasing the dynamic change in feedbackvariables (arterial P_(CO2) and P_(O2)) when alveolar ventilationchanges dynamically. As well, such an increase in lung volume decreasesthe end-expiratory length of inspiratory muscles, thereby decreasingtheir force generation during inspiration. Together, both effects ofnasal CPAP decrease the loop gain. When CPAP pressure is dynamicallyvaried in synchrony with the periodic breathing cycle, both effectsdynamically modulate loop gain. However, experience indicates that, overthe range of CPAP pressure of 1-10 cm H₂O, these produce a smallerdecrease in loop gain than varying V_(D). Additionally, dynamic changesin V_(D) are less likely to disturb the sleeper than changes in CPAPpressure. Accordingly, the use of increase in CPAP pressure to decreaselung volume and, thereby, decrease loop gain, represents a supplementarystrategy of the present invention.

[0077] The patient with central sleep apnea or combined central andobstructive sleep apnea sleeps with a nasal CPAP mask sealed to the face(FIGS. 2, 4A, 4B, 5, 6, 7). Mouth leaks, if present, are eliminated by achin strap and/or an oral appliance combined with nasal occlusion. Ifthis is not adequate, the nose mask is replaced with a full face mask.The patient interface is connected to a positive pressure outlet of alow impedance blower by a tubing, in one embodiment typically 2-3 cm indiameter and 1.5 m long. The bias flow exits the patient interfaceeither through an orifice of fixed, selectable size (FIGS. 4A, 4B, 5, 6,7) or through a tubing, in one embodiment (1.5 m long, 1 cm in diameter)connected to a computer-controlled variable resistor (FIG. 2). In such asystem, the patient interface pressure is determined by blower RPM, andthe rate of bias flow V _(B) is the resultant of patient interfacepressure and patient interface outflow resistance. The apparatus shownin FIGS. 2 and 4B includes a pneumotachagraph for measuring flow fromthe blower. This device is suitable for initial titration or for nightlytherapeutic use. Also, a CO₂ meter can be added with a sampling catheterconnected to the patient interface. This allows monitoring of end-tidaland inspired F_(CO2). The device shown in FIG. 4A is a simpler versionof that shown in FIG. 4B and is suitable for nightly use.

[0078] The dynamically variable bias flow device (FIG. 2) allowsmoment-to-moment adjustment of bias flow with negligible changes inpatient interface pressure. The exhaust resistor can be controlled by anindependent observer during a polysomnographic study, or it can beautomatically controlled by a computer algorithm. The control ofexternal dead space volume (V_(ED)) is either passively adjusted withthe exhaust resistance being constant, or actively adjusted with exhaustresistance being varied in time. In the passive adjustmentimplementation, bias flow is constant in time since a fixed exhaustorifice is used. In the active adjustment, bias flow changes in timeowing to the change in resistance of the bias flow resistor.

[0079]FIG. 8 depicts airflow recorded in the tubing which connects theblower to the patient interface. Positive values signify airflow fromthe blower to the patient interface, and negative values indicateairflow from the patient interface to the blower. The former is referredto as “wash” airflow since it eliminates expired gas from the patientinterface; the latter is referred to as “retrograde” airflow since itrepresents expired air flowing in the reverse direction to that whichnormally occurs during CPAP administration. As shown in FIG. 8A (toppanel), airflow in the tubing is equal to the sum of two air flows, V_(B) and respiratory airflow. The former is constant and the lattervaries with the respiratory cycle. Inspiratory airflow produces anupward deflection in V and expiratory airflow produces a downwarddeflection in V. At the end of expiration (upward arrow in FIG. 8A),respiratory airflow equals zero and tubing airflow equals bias airflowwhich is chosen to be 1.0 L/sec in this example. Peak expiratory airflowoccurs early in expiration (downward arrow in FIG. 8A) and equals 1.0L/sec in this example. At this time, tubing airflow is zero because peakexpiratory airflow equals V _(B).

[0080]FIGS. 8A, 8B, 8C, 8D, 8E and 8F depict the changes in tubingairflow that occur as V _(B) is progressively reduced from 1.0 L/sec(FIG. 8A) to 0.15 L/sec (FIG. 8F). Respiratory airflow is held constantthroughout. As V _(B) is reduced from 1.0 to 0.5, 0.35, 0.25, 0.20 and0.15 L/sec (FIGS. 8A, 8B, 8C, 8D, 8E, 8F), retrograde airflow appearsduring expiration and becomes progressively larger. The volume of airwhich moves retrogradely during expiration (V_(ret), hatched area)increases progressively as V _(B) is decreased. Conversely, the volumeof air which moves from the blower to the patient interface duringexpiration (V_(wash), stippled area) decreases as V _(B) is decreased.

[0081] The volume of air resident in the patient interface and tubing atthe end of expiration (downward arrow, FIG. 8A) is referred to asresidual volume (V_(R)). V_(R) can be estimated as the differencebetween V_(RET)−V_(WASH).

V _(R) =V _(RET) −V _(WASH)  (Equation 4)

[0082] In the first five examples shown in FIG. 3, V_(R) is negative orequal to zero (FIGS. 8A, 8B, 8C, 8D, 8E), signifying that with thisrespiratory pattern, there is no added dead space (V_(ED)=0). However,if pulmonary ventilation were to increase, V_(RET) would increase andV_(R) would become positive. Similarly, if the duration of expiration(T_(e)) were to decrease, V_(WASH) would decrease and V_(R) would becomepositive. When breathing is stimulated by an increase in arterialP_(CO2) and a decrease in arterial P_(O2), tidal volume increases andT_(e) decreases. Accordingly, if V_(B) is relatively low (0.35 and 0.25in this example), chemical stimulation will cause V_(R) to assume apositive value so that higher levels of pulmonary ventilation will beassociated with greater values of V_(R).

[0083] The presence of a positive value for V_(R) indicates that V_(ED)will assume a finite value (FIG. 8F). However, V_(R) does not equalV_(ED). During inspiration, gas resident in the patient interface andtubing flows to one of two places, namely: out the exhaust port or intothe respiratory tract. Only the latter constitutes V_(ED). Accordingly,a fraction of V_(R) will be inspired, that fraction depending on thevalue of V _(B) relative to the inspiratory flow rate. Use of a highvalue of V _(B) will minimize V_(ED). Thus, chemical stimulation ofbreathing causes three changes in the respiratory pattern, an increasein expiratory air flow rate, a decrease in Te, and an increase ininspiratory air flow rate, each of which acts independently to augmentV_(ED). Together, they cause a sharp rise in V_(ED) when V_(E) increasesby chemical stimulation if the V _(B) is relatively low. FIG. 8Billustrates the time in expiration when the tubing and patient interfaceare flushed by fresh, room air. This time is expressed as a fraction ofT_(e) and referred to as T_(FRAC). T_(FRAC) increases progressively as V_(B) decreases. When T_(FRAC) equals 100%, a critical value of V _(B)has been reached; further decreases in V _(B) will produce a finitevalue of V_(ED).

[0084] To calculate V_(ED), the following relationship is used:

V _(ED) =V _(R)−( V _(B))(t′)  (Equation 5)

[0085] where t′ defines the time required for V_(R) to be eliminatedfrom the patient interface and conducting tubing as shown in FIG. 9.V_(ED) can be calculated by progressively incrementing inspiratory time(t) from zero (the onset of inspiration) and calculating V_(SUM)inspired volume plus exhaust port volume, i.e.,

V _(SUM)=∫₀ _(t) V ₁+∫₀ ^(t) V _(B)  (Equation 6)

[0086] where V₁ represents inspiratory flow rate, i.e., total flow minusbias flow during inspiration. The incrementing procedure continues untilV_(SUM) equals V_(R).

[0087]FIG. 9 depicts the changes in V_(RET) and V_(ED) that occur whenpulmonary ventilation is stimulated by increasing arterial P_(CO2). V_(B) is assumed to equal 0.25 L/sec in all cases, and is approximatelytwo times resting V _(A)(5.7 L/min). FIG. 8D depicts the respiratorypattern under unstimulated, resting conditions (V _(E)=8.0 L/sec). Whenventilation is mildly stimulated (V _(E)=15.0 L/sec, FIG. 9A), V_(RET)increases and V_(WASH) decreases so that V_(ED) equals 0.26 L. Furtherstimulation of breathing (FIG. 9B) results in V_(ED) equal to 0.47 Lwhen V _(E) equals 19.5 L/sec, V_(ED) equal to 0.79 L when V _(E) equals25.7 L/sec (FIG. 9C) and V_(ED) equal to 1.19 L when V_(E) equals 36.7L/sec (FIG. 9D). Note that T_(FRAC) increases progressively as V _(E)increases for a constant V _(B).

[0088] The dependence of V_(RET), V_(ED) and T_(FRAC) on V _(E) is shownin FIGS. 10, 11 and 12, respectively, for all four values of V _(E).Each plot shows a family of V _(B) isopleths. V_(RET), V_(D) andT_(FRAC) show a quasi-linear increase as V_(E) increases (FIGS. 10, 11,12 and 13).

[0089]FIG. 13 illustrates the relationship between V _(A) and V _(E) atthe five levels of V _(B). For values of 1.0 L/sec and greater, allpoints lie on a monotonically ascending curve. However, for lower valuesof V _(B), the relationship is shifted downward, indicating that anincrement in V _(E) caused by an increase in chemical stimulus willcause a smaller increment in V _(A). This implies a reduction in loopgain which can be quantitated as the change in slope of thisrelationship. Note that at values of V _(E) equal to 0.35 L/sec less, V_(A) becomes constant for values of V _(E) greater than 15 L/sec. Inother words, the invention clamps V _(A) at some maximal value.

[0090]FIG. 14 illustrates the overall dependence of loop gain on theratio, log V _(E)/V _(A). This ratio, calculated for resting breathing,provides a normalized index of V _(E) for any patient. The relationshipis plotted over the range of log V _(E)/V _(A) from 0 to 1., i.e. overthe range of variation in V _(E) where V_(ED) is less than zero underresting conditions. Note that the loop gain decreases steeply as restingV_(RET)/V_(WASH) decreases from 0.5 to 0. For this reason, we select aratio value of 0.3 for usual application of the method in treatingcentral sleep apnea. In this situation, V _(B) is approximately twotimes V _(A) and T_(FRAC) equals 80%. This value results in a 50%decrease in loop gain while providing more than adequate washout ofexpired gases from the apparatus under resting conditions. Accordingly,loop gain is reduced to a value that stabilizes breathing for manypatients with central sleep apnea without any risk of adding externaldead space when the patient is breathing normally and having no centralsleep apnea.

[0091] The goal of the passive dead space method is to apply nasal CPAPwith a V _(B) sufficient to produce V_(ED)=0 under resting conditions,but such that the V_(ED) will increase with increasing V _(E) sufficientto reduce the loop gain and stabilize breathing. Specifically, duringhypopnea or normal breathing, the apparatus produces no gas exchangeinefficiency in breathing. However, during hyperpnea, V _(ED) increasesprogressively as V _(E) rises above normal. The net effect is that V_(D)is dynamically adjusted in keeping with variations in V _(E) such thatthe periodic fluctuation in V _(A) is attenuated. This means thatfluctuations in arterial P_(O2) and P_(CO2) are reduced, so that loopgain of the system is reduced. This acts to stabilize breathing.

[0092] The advantage of the passively adjusting dead space device isthat loop gain can be reduced by a relatively simple apparatus requiringno active algorithmic, dynamic adjustment in V _(B). Once the effectiveV _(B) has been determined, this can be achieved by permanent adjustmentof the resistance of the exhaust port of the patient interface, therebyeliminating the need for an exhaust tubing and computer-controlledexhaust resistor. However, if the loop gain of the patient's respiratorycontrol system is very high, the passive apparatus may not reduce theloop gain sufficiently to stabilize breathing. In that case, adynamically adjusting V_(ED) apparatus is employed. In the embodimentthat dynamically adjusts V _(B), the indicator variables (V_(RET),V_(WASH), T_(frac) and V_(B)/V_(A)) are calculated on line. Periodicbreathing is detected either by the recurrence of apneas or byautoregressive analysis. V _(B) is reduced progressively until evidenceof central sleep apnea is eliminated or until the indicator variablesreach their critical limits (V_(RET), V_(WASH)=0.8, T_(frac)=80% and V_(B)/V _(A)=2).

[0093]FIG. 19 depicts another embodiment of the invention. The patientwith central sleep apnea wears a full face mask 220 which can be loosefitting, but should be leak resistant such as by using an oral interfacewith nasal occlusion. The mask 220 is purged by a bias flow from ahigh-impedance blower 222 which supplies a constant rate of airflow tothe mask. This bias flow is selectable and rapidly adjustable by thecontrolling computer 224. The bias flow exits to the atmosphere througha low-resistance reservoir tubing 226. The respiratory airflow (bothinspiration and expiration) occurs through this reservoir tubing.Because of the tubing's low resistance, the mask pressure remains nearatmospheric pressure. A pneumotachograph (flow meter 228) in thereservoir tubing allows monitoring of bias flow and respiration airflowand calculation of wash volume during expiration and expired tidalvolume.

[0094] Under resting conditions or when no central sleep apnearespiration is detected, bias flow is held relatively high so that washvoluke exceds the volume of gas expired into the tube. Accordingly, wheninspiration begins, the reservoir tube has been washed completely withbias flow, and the patient inspires room air. Thus, no external deadspace has been added when the patient is breathing normally and noventilatory periodicity is detected by the computer. When the computer222 detects ventilatory periodicity, bias flow is varied in synchronywith the periodicity. Specifically, when instantaneous ventilation isgreater thant he moving average, bias flow is reduced so that washvolume is less than expired tidal volume. This causes rebreathing anddecreases loop gain of the system. During periods of underbreathing,bias flow is maintained at high values so that no rebreathing occurs.The volume of gas resident in the reservoir tubing 226 at the end ofexpiration (i.e., the rebreathing volume) is calculated on line and isadjusted to be proportional to the difference between instantaneousventilation and moving average ventilation. Thus, dead space increasesprogressively as overbreathing occurs, thereby minimizing the effect ofthe excessive ventilation on arterial blood gases. This, in turn,minimizes the duration of the apnea or magnitude of hypopnea thatfollows the overbreathing and stabilizes ventilation.

[0095] It will be appreciated by those of ordinary skill in the art thatthe invention can be implemented in other specific forms withoutdeparting from the spirit or central character thereof. The presentlydisclosed embodiments are therefore considered in all respects to beillustrative and not restrictive. The scope of the invention isindicated by the appended claims rather than the foregoing description,and all changes which come within the meaning and range of equivalencethereof are intended to be embraced herein. Accordingly, the abovedescription is not intended to limit the invention, which is to belimited only by the following claims.

1. An apparatus for treating a breathing disorder comprising: a gassupplying means; and a leak resistant patient interface operablyconnected using a tube to the gas supplying means, the leak resistantpatient interface having an exit, wherein the apparatus is arranged suchthat during periods of increased breathing associated with the breathingdisorder, some exhaled gasses from the patient flow retrograde into thetube towards the gas supplying means and away from the exit; wherein theapparatus is adapted such that during an initial exhale portion ofincreased breathing associated with the breathing disorder, some exhaledgasses from the patient flow retrograde into the tube towards the gassupplying means and away from the exit and wash flow out of the tubesuch that during a next inhale portion a sufficient amount ofrebreathing occurs to control the breathing disorder.
 2. The apparatusof claim 1, wherein the leak resistant patient interface comprises anoral interface and nasal occlusion device.
 3. The apparatus of claim 2,wherein the apparatus is adapted such that during normal breathingperiods little rebreathing occurs.
 4. The apparatus of claim 3, whereinthe apparatus is adapted such that during normal breathing periods someretrograde flow occurs but wash flow is sufficient to remove exhaled airbefore a next inhale portion.
 5. The apparatus of claim 4, wherein theretrograde flow into the tube is influenced by gas pressure from the gassupplying means and by an exit hole size.
 6. An apparatus for treating abreathing disorder comprising: a gas supplying means; and a leakresistant patient interface operably connected using a tube to the gassupplying means, the leak resistant patient interface having an exit,wherein the apparatus is arranged such that during periods of increasedbreathing associated with the breathing disorder, some exhaled gassesfrom the patient flow retrograde into the tube towards the gas supplyingmeans and away from the exit, wherein gas pressure from the gassupplying means is set at a controlled level below four cm H₂O pressureindependently of the respiratory cycle of the patient.
 7. The apparatusof claim 6, wherein the leak resistant patient interface comprises anoral interface and nasal occlusion device.
 8. The apparatus of claim 7,wherein a size of the exit size is adjustable.
 9. The apparatus of claim8, wherein pressure in the leak resistant patient interface is set highenough to treat obstructive sleep apnea.
 10. The apparatus of claim 9,wherein the gas-supplying means comprises a blower which blows air tothe leak resistant patient interface.
 11. The apparatus of claim 6,wherein the leak resistant patient interface is adapted to fit about apatient's nose.
 12. The apparatus of claim 6, wherein the gas-supplyingmeans is adjustable.
 13. A method of treating a patient suffering from abreathing disorder, the method comprising: providing an apparatuscomprising a gas supplying means and a leak resistant patient interfaceadapted to be fit on the patient's airway, the leak resistant patientinterface operably connected using a tube to the gas supplying means,the leak resistant patient interface having an exit; fitting the leakresistant patient interface to the patient; and adjusting the apparatussuch that during periods of increased breathing associated with thebreathing disorder, some exhaled gasses from the patient flow retrogradeinto the tube, wherein the adjusting step is done such that during aninitial exhale portion of increased breathing associated with thebreathing disorder, some exhaled gasses from the patient flow retrogradeinto the tube and wash flow out of the tube such that during a nextinhale portion some rebreathing occurs sufficient to treat the breathingdisorder.
 14. The method of claim 13, wherein the leak resistant patientinterface comprises a dental appliance and a nasal occlusion device, andfitting the leak resistant patient interface to the patient comprises:fitting the dental appliance to the mouth of the patient; and blockingthe patient's nose with the nasal occlusion device.
 15. The method ofclaim 14, wherein the adjusting step is done such that during normalbreathing periods little rebreathing occurs.
 16. The method of claim 15,wherein the adjusting step is done such that during normal breathingperiods some retrograde flow occurs but wash flow is sufficient toremove exhaled air before a next inhale portion.
 17. The method of claim14, wherein the retrograde flow into the tube is influenced by gaspressure from the gas supplying means and by an exit hole size.
 18. Amethod of treating a patient suffering from a breathing disorder, themethod comprising: providing an apparatus comprising a gas supplyingmeans and a leak resistant patient interface adapted to be fit on thepatient's airway, the leak resistant patient interface operablyconnected using a tube to the gas supplying means, the leak resistantpatient interface having an exit; fitting the leak resistant patientinterface to the patient; and adjusting the apparatus such that duringperiods of increased breathing associated with the breathing disorder,some exhaled gasses from the patient flow retrograde into the tubewherein the adjusting step is such that gas pressure from the gassupplying means is set at a level below four cm H₂O pressureindependently of the respiratory cycle of the patient.
 19. The method ofclaim 18, wherein the leak resistant patient interface comprises adental appliance and a nasal occlusion device, and fitting the leakresistant patient interface to the patient comprises: fitting the dentalappliance to the mouth of the patient; and blocking the patient's nosewith the nasal occlusion device.
 20. (Canceled)
 21. The method of claim19, wherein the adjusting step includes adjusting an exit hole size. 22.The method of claim 19, wherein pressure in the leak resistant patientinterface is set high enough to treat obstructive sleep apnea.
 23. Themethod of claim 19, wherein the gas supplying means comprises a blower.24. An apparatus for treating a breathing disorder comprising: a gassupplying means; a leak resistant patient interface adapted to be fit ona patient's airway, the leak resistant patient interface operablyconnected using an input tube to the gas supplying means, the leakresistant patient interface having an exit; a variable air resistancemeans operably connected to the exit of the leak resistant patientinterface; and a controller operably connected to the variable airresistance means to adjust a level of rebreathing that occurs andmaintain a temporally variable flow of air in the input tube withoutproducing significant deviations in leak resistant patient interfacepressure.
 25. The apparatus of claim 24, wherein the leak resistantpatient interface comprises an oral interface and nasal occlusiondevice.
 26. The apparatus of claim 25, wherein the variable airresistance means comprises an adjustable valve.
 27. The apparatus ofclaim 26, further comprising an exit tube between the leak resistantpatient interface and the adjustable valve.
 28. The apparatus of claim25, wherein the controller adjusts the variable air resistance means toprovide a dead space during certain portions of a sleep cycle.
 29. Theapparatus of claim 25, wherein the controller adjusts the variable airresistance means to modify exit flow out of the leak resistant patientinterface at different times during a night's sleep.
 30. The apparatusof claim 25, further comprising a flow meter adapted to provide signalsto the controller.
 31. The apparatus of claim 25, wherein the controllerdetects periodicities in sleep cycle to determine how to adjust thelevel of rebreathing. 32-35. (Canceled)
 36. An apparatus for treating abreathing disorder comprising: a blower; a leak resistant patientinterface adapted to be fit on a patient's airway, the leak resistantpatient interface incorporating a dental appliance to reduce mouth leaksand a nasal occlusion device to eliminate nose leaks, the leak resistantpatient interface operably connected using a tube to the gas supplyingmeans; and a processor adapted to adjust a level of rebreathing tocontrol the breathing disorder in the patient by adjusting an activecontrol element of the apparatus.
 37. The apparatus of claim 36, whereinthe active control element is a variable air resistance means operablyconnected to a exit of the leak resistant patient interface.
 38. Theapparatus of claim 36, wherein the active control element is a unit toadjust a blower output.
 39. The apparatus of claim 38, wherein theactive control element is a unit to adjust a blower output revolutionsper minute.
 40. The apparatus of claim 38, further comprising an exittube connected to the leak resistant patient interface.
 41. Theapparatus of claim 36, wherein the active control element is arecirculator.
 42. The apparatus of claim 36, wherein the active controlelement is a valve to a dead space volume.
 43. The apparatus of claim36, wherein the active control element is adjusted during a periodicsleep cycle of the patient.
 44. The apparatus of claim 36, wherein theactive control element is adjusted over an entire sleeping period. 45.The apparatus of claim 36, wherein the processor receives data from aflow meter or a carbon dioxide sensor.
 46. (Canceled)
 47. An apparatusfor treating a breathing disorder comprising: a blower; and a leakresistant patient interface adapted to be fit on a patient's airway, theleak resistant patient interface operably connected using a tube to theblower, the leak resistant patient interface having an exit, theresistance of the exit being set such that during treatment of thebreathing disorder in the patient, expiratory air from the patient flowsthrough the tube towards the blower and away from the exit, wherein theapparatus is arranged such that a gas flow from the blower is less thanthat used to treat obstructive sleep apnea.
 48. The apparatus of claim47, wherein the leak resistant patient interface comprises an oralinterface and nasal occlusion device.
 49. The apparatus of claim 48,wherein gas pressure from blower is set at four cm H₂O pressure orbelow.
 50. (Canceled)
 51. The apparatus of claim 48, wherein theapparatus is arranged such that during periods of increased breathingassociated with the breathing disorder, some exhaled gasses from thepatient flow retrograde into the tube.
 52. The apparatus of claim 51,wherein the apparatus is adapted such that during an initial exhaleportion of increased breathing associated with the breathing disorder,some exhaled gasses from the patient flow retrograde into the tube andwash flow out of the tube such that during a next inhale portion somerebreathing occurs.
 53. The apparatus of claim 51, wherein the apparatusis adapted such that during normal breathing periods little rebreathingoccurs.
 54. The apparatus of claim 51, wherein the apparatus is adaptedsuch that during normal breathing periods some retrograde flow occursbut wash flow is sufficient to remove exhaled air before a next inhaleportion.
 55. The apparatus of claim 48 wherein the blower is adjustable.56. A method of treating a patient suffering from a breathing disorder,the method comprising: providing an apparatus comprising a blower and aleak resistant patient interface adapted to be fit on the patient'sairway, the leak resistant patient interface operably connected using atube to the blower, the leak resistant patient interface having an exit;fitting the leak resistant patient interface to the patient's airway;and adjusting the apparatus such that gas flow from the blower iscontrolled at a variable flow rate and essentially constant pressure,the pressure being less than that used to treat obstructive sleep apnea,in order to treat the breathing disorder in the patient.
 57. The methodof claim 56, wherein the leak resistant patient interface comprises adental appliance and a nasal occlusion device, and fitting the leakresistant patient interface to the patient comprises: fitting the dentalappliance to the mouth of the patient; and blocking the patient's nosewith the nasal occlusion device.
 58. The method of claim 57, wherein theadjusting step is such that gas pressure from the blower is set belowfour cm H₂O pressure.
 59. (Canceled)
 60. The method of claim 57, whereinthe adjusting step is such that during periods of increased breathingassociated with the breathing disorder, some exhaled gasses from thepatient flow retrograde into the tube.
 61. The method of claim 60,wherein the adjusting step is done such that during an initial exhaleportion of increased breathing associated with the breathing disorder,some of the patient's exhaled gasses flow retrograde into the tube andwash flow out of the tube such that during a next inhale portion somerebreathing occurs.
 62. The method of claim 60, wherein the adjustingstep is done such that during normal breathing periods littlerebreathing occurs.
 63. The method of claim 62, wherein the adjustingstep is done such that during normal breathing periods some retrogradeflow occurs but wash flow is sufficient to remove the exhaled air beforea next inhale portion.
 64. The method of claim 57, wherein theretrograde flow into the tube is influenced by gas pressure from theblower and by a size of the exit. 65-76. (Canceled)
 77. A methodcomprising: providing an apparatus comprising a blower and a leakresistant patient interface adapted to be fit on a patient's airway, theleak resistant patient interface operably connected using a tube to theblower, the leak resistant patient interface having an exit, theresistance of the exit being set that during treatment of a breathingdisorder in the patient, expiratory air from the patient flows throughthe tube towards the blower and away from the exit; fitting the leakresistant patient interface to the patient's airway; treating anobstructive sleep apnea with the apparatus; adjusting the apparatus totreat the breathing disorder; and treating obstructive sleep apnea withthe apparatus
 78. The method of claim 77 in which the leak resistantpatient interface comprises a dental appliance and a nasal occlusiondevice, and fitting the leak resistant patient interface to the patientcomprises: fitting the dental appliance to the mouth of the patient; andblocking the patient's nose with the nasal occlusion device
 79. Themethod of claim 78, wherein the adjusting step comprises adjusting theapparatus such that gas flow from the blower is less than that used totreat obstructive sleep apnea to treat the breathing disorder in thepatient.
 80. The method of claim 78, wherein the adjusting step is suchthat gas pressure from the blower is set below four cm H₂O pressure. 81.(Canceled)
 82. The method of claim 78 wherein the adjusting step is suchthat during periods of increased breathing associated with the breathingdisorder, some of the patient's exhaled gasses flow retrograde into thetube.
 83. The method of claim 82, wherein the adjusting step is donesuch that during an initial exhale portion of increased breathingassociated with the breathing disorder, some exhaled gasses from thepatient flow retrograde into the tube and wash flow out of the tube suchthat during a next inhale portion some rebreathing occurs.
 84. Themethod of claim 82, wherein the adjusting step is done such that duringnormal breathing periods little rebreathing occurs.
 85. The method ofclaim 84, wherein the adjusting step is done such that during normalbreathing periods some retrograde flow occurs but wash flow issufficient to remove exhaled air before a next inhale portion.
 86. Themethod of claim 78, wherein the retrograde flow into the tube isinfluenced by gas pressure from the blower and by a size of the exithole.
 87. The method of claim 78, wherein the obstructive sleep apneatreating step comprises supplying blower pressure greater than eight cmH₂O.
 88. The method of claim 78, wherein the obstructive sleep apneatreating step occurs before the adjusting step.
 89. The apparatus ofclaim 1, wherein gas pressure from the gas supplying means is set belowfour cm H₂O pressure.
 90. (Canceled)
 91. The method of claim 13, whereinthe adjusting step is such that gas pressure from the gas supplyingmeans is set below four cm H₂O pressure.
 92. (Canceled)